Real-Time Monitoring of New Delhi Metallo-?-Lactamase Activity in Living Bacterial Cells by (1) H NMR Spectroscopy.
Related Articles Real-Time Monitoring of New Delhi Metallo-?-Lactamase Activity in Living Bacterial Cells by (1) H NMR Spectroscopy.
Angew Chem Int Ed Engl. 2014 Jan 23;
Authors: Ma J, McLeod S, Maccormack K, Sriram S, Gao N, Breeze AL, Hu J
Abstract
Disconnections between in vitro responses and those observed in whole cells confound many attempts to design drugs in areas of serious medical need. A method based on 1D (1) H NMR spectroscopy is reported that affords the ability to monitor the hydrolytic decomposition of the carbapenem antibiotic meropenem inside Escherichia coli cells expressing New Delhi metallo-?-lactamase subclass 1 (NDM-1), an emerging antibiotic-resistance threat. Cell-based NMR studies demonstrated that two known NDM-1 inhibitors, L-captopril and ethylenediaminetetraacetic acid (EDTA), inhibit the hydrolysis of meropenem in vivo. NDM-1 activity in cells was also shown to be inhibited by spermine, a porin inhibitor, although in an in vitro assay, the influence of spermine on the activity of isolated NDM-1 protein is minimal. This new approach may have generic utility for monitoring reactions involving diffusible metabolites in other complex biological matrices and whole-cell settings, including mammalian cells.
PMID: 24458501 [PubMed - as supplied by publisher]
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